1) Peptic ulcers are caused by an imbalance between aggressive factors like gastric acid and protective factors in the stomach and duodenum. 2) Anti-ulcer drugs work by decreasing gastric acid secretion, enhancing mucosal protection, or eradicating the H. pylori bacteria responsible for many ulcers. 3) Common classes of anti-ulcer medications include H2 receptor antagonists, proton pump inhibitors, antacids, and anti-H. pylori drugs. H2 receptor antagonists and proton pump inhibitors reduce acid by blocking histamine and the proton pump, while antacids neutralize existing acid.

1. Anti-ulcer Drugs
Zulcaif Ahmad

2. Introduction
 Peptic /stomach ulcer is the condition in which imbalance of
aggressive factor and defensive factors.
 From ancient time stomach ulcer has been recognized and also
therapy established according to their knowledge.
 A Roman emperor Marcus Aurelius, whose death has been
attributed by some to a perforated ulcer.
 More than 12 centuries ago, Paulus Aeginata who recognized that
acid – neutralization was the effective treatment.
 Later in starting of 19 century the lot of research has been
developed for the treatment of ulcer.

3. Continue….
 After period of time it has been identified that bacteria can
causes the ulcer.
 Mainly Helicobacter pylori found to be recurrence of stomach
ulcer.
 The main goal of anti-ulcer drug is that to decreasing the level
of gastric acidity or enhancing mucosal protection.
 For infectious agent new approaches was found in order to
prevention of infection or removal of micro organism.

4. PHYSIOLOGY OF GASTRIC ACID
SECERTION
 Gastric acid secretion is a complex, continuous process in which
multiple central and peripheral factors contribute to a common
endpoint: the secretion of H+ by parietal cells.
 Neuronal (acetylcholine, ACh), paracrine (histamine), and
endocrine (gastrin) factors all regulate acid secretion .
 Their specific receptors (M3, H2, and CCK2 receptors, respectively)
are on the basolateral membrane of parietal cells in the body and
fundus of the stomach.

5.  The H2 receptor is a GPCR that activates the Gs-
adenylylcyclase-cyclic AMP-PKA pathway.
 ACh and gastrin signal through GPCRs that couple to the
Gq-PLC-IP3-Ca2+ pathway in parietal cells.
 In parietal cells, the cyclic AMP and the Ca 2+-dependent
pathways activate H+,K+-ATPase (the proton pump), which
exchanges hydrogen and potassium ions across the
parietal cell membrane.

7. What is Peptic Ulcer?
 Peptic /stomach ulcer
is the condition in
which imbalance of
aggressive factor and
defensive factors.
 Aggressive factor :
Gastric acid, gastrin,
pepsin
 Defensive factor :
Prostaglandin, mucosa,
bicarbonate

8. •Abdominal pain,
classically epigastric
with severity relating
to mealtimes, after
around 3 hours of
taking a meal.
•Loss of appetite and
weight loss.
•Waterbrash (rush of
saliva after an episode
of regurgitation to
dilute the acid in
esophagus);
•Nausea, and copious
vomiting

9. Complications
 Gastrointestinal bleeding is the most common
complication. Sudden large bleeding can be life-
threatening. It occurs when the ulcer erodes one of
the blood vessels.
 Perforation (a hole in the wall) often leads to
catastrophic consequences. Erosion of the gastro-
intestinal wall by the ulcer leads to spillage of
stomach or intestinal content into the abdominal
cavity. Perforation at the anterior surface of the
stomach leads to acute peritonitis, initially
chemical and later bacterial peritonitis. The first
sign is often sudden intense abdominal pain.
Posterior wall perforation leads to pancreatitis;
pain in this situation often radiates to the back.
 Penetration is when the ulcer continues into
adjacent organs such as the liver and pancreas.
 Scarring and swelling due to ulcers causes
narrowing in the duodenum and gastric outlet
obstruction. Patient often presents with severe
vomiting.

10. Classification Of Antiulcer Agent
1) Reduction of gastric acid secretion
 H2 antihistamines: Cimetidine, ranitidine, famotidine, roxaatidine, loxatidine
 PPI’s : Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole
 Anticholinergics: Pirenzepine, propantheline, oxyphenonium
 Prostaglandine analogues:- Misoprostol, enprostil, rioprostil
2) Neutralization of gastric acid (Antacids)
 Systemic : Sodium bicarbonate, sod.citrate
 Nonsystemic (Local) : Mg hydroxide, Mg trisilicate, Al hydroxide gel, calcium
carbonate
3) Ulcer protectives: Sucralfate, CBS ( Colloidal Bismuth Subcitrate)
4) Ulcer healing drugs: Carbenoxolone sod.
5) Anti-H. pyloric drugs: Amoxicillin, clarithromycin, metronidazole, tinidazole,
tetracycline

11. Histamine: H2 Receptor Antagonist
 Histamine receptor on parietal cells
Autonomic system: food stimulates gastrin release, gastrin
stimulates histamine release, histamine
stimulates parietal cells secretion of HCl.
MECHANISM OF ACTION
 The H2 receptor antagonists inhibit acid production by
reversibly competing with histamine for binding to H2
receptors on the basolateral membrane of parietal cells.
 Block histamine from stimulating the acid-secreting parietal cells
of the stomach.
 H2 antagonist mainly basal, psychic, neurogenic, gastric
secretion is suppressed and other stimuli Ach, gastrin, alcohol,
food also inhibited.

12.  Reversible competitive inhibitors of H2 receptor.
 Highly selective for H2 receptors.
 Very effective in inhibiting nocturnal acid secretion
( as it depends largely on Histamine ).
 Modest impact on meal stimulated acid secretion (As
it depends on gastrin, acetylcholine and histamine).

13. Pharmacokinetics
Absorbed rapidly and completely except for
famotidine; food and antiacids may reduce
absorption; distributed widely throughout the
body; metabolized by the liver; excreted primarily
in the urine.

14. Cimetidine Ranitidine
Bioavailability 80 50
Relative Potency 1 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4
Duration of 6 8
action (hrs)
Inhibition of 1 0.1
CYP 450
Dose mg(bd) 400 150

15. Therapeutic Uses
Used therapeutically to:
Promote healing of duodenal and gastric ulcers.
Provide long-term treatment of pathological GI
hypersecretory conditions.
Reduce gastric acid production and prevent
stress ulcers.

16. Adverse effect, Interaction, Contraindication
 Adverse effect
 Headache
 Dizziness
 Bowel upset
 Cimetidine causes gynecomastia, galactorrhea(as it is
antiandrogenic & increases prolactin level)
 Interaction
 Inhibits CYP-450 leads to inhibits the metabolism of many
drugs so that they accumulate to toxic level.
e.g. theophylline,warfarin, phenytoin, quinidine
 Contraindication
 Renal impairment
 Hepatic failure

17. Proton Pump Inhibitors
(PPIs)
 Disrupt chemical binding in stomach cells to reduce acid
production, lessening irritation and allowing peptic ulcers to
heal.
 These drugs include:
 Omeprazole
 Rabeprazole
 Pantoprazole
 Lansoprazole
 Esomaprazole
MECHANISM OF ACTION OF PPIs.
Block the last step in the secretion of gastric
acid by combining with hydrogen, potassium,
and adenosine triphosphate in the parietal cells
of the stomach.

18. Continued MOA….
 Most effective drugs in antiulcer therapy.
 Irreversible inhibitor of H+ K+ ATPase to apical membrane of the
parietal cell.
 Prodrugs requiring activation in acid environment.
 Inactivate at neutral pH, at pH<5 rearranges to 2 charged cationic
form- sulphenic acid & sulphenamide.
 React covalently with –SH groups of the H+ K+ ATPase enzyme.
 Weakly basic drugs & so accumulate in canaliculi of parietal cell.
 Activated in canaliculi & binds covalently to extracellular domain of
H+ K+ ATPase.
 Acid secretion resumes only after synthesis of new molecules.

19. o Pharmacokinetic
Bioavailability : ~50% (instability at acidic pH)
Metabolism : In Liver (CYP2C19 and CYP3A4).
Excretion : Metabolites excreted through renally
Onset action : ½-1 hour
Duration of action : 24 hours
 Adverse effect
 Hepatic dysfunction
 Dizziness
 Nausea
 Headache
 Interaction
 Inhibits oxidation of certain drugs : diazepam,
phenytoin, warfarin

20. Antacid
These are the basic substances which neutralize gastric
acidity.
Acid neutralizing capacity: no.of mEq of 1N HCl that
brought to pH 3.5 in 15 min. by a unit dose of the
antacid preparation.
 Systemic antacid :
 Sodium bicarbonate, water soluble, acts i.v. duration of
action is short.
 Potent neutralizer, pH may rises above 7.
 Produces CO2 in stomach leads to distention,
discomfort.
 Increases sodium load leads to worsen in CHF with
edema.
 Large dose produces alkalosis.

21.  Non-systemic antacid:
 These are insoluble and poorly absorbed basic compound.
 React in stomach with acid to form respective chloride
salts.
 This again reacts with bicarbonate is not spared for
absorption, hence no acid –base disturbance.
 Aluminium hydroxide gel:
 The Al+³ ions relaxes smooth muscle leads to delay in
gastric emptying.
 This causes constipation.
 Mucosal astringent reaction also leads to constipation.

22. Ulcer Protectives - Sucralfate
Sucralfate consists of the octasulfate of sucrose to
which Al(OH)3 has been added.
 In an acid environment(pH <4), sucralfate undergoes
extensive cross-linking to produce a viscous, sticky
polymer that adheres to epithelial cells and ulcer
craters for up to 6 hours after a single dose.
In addition to inhibiting hydrolysis of mucosal
proteins by pepsin, sucralfate may have additional
cytoprotectiveeffects, including stimulation of local
production of prostaglandins and epidermal growth
factor.

23. Since it is activated by acid, sucralfate should be taken
on an empty stomach 1 hour before meals.
The use of antacids within 30 minutes of a dose of
sucralfate should be avoided.
The usual dose of sucralfate is 1 g four times daily
(for active duodenal ulcer) or 1 g twice daily (for
maintenance therapy).

24. Anti H.pylori drugs
 H pylori: Spiral-shaped,pH-sensitive,
gram –ve bacteria.
It attaches to the surface epithelium
beneth the mucus.
Has high urease activity
Produces ammonia which maintains
a neutral microenvironment around
the bacteria.

25. Promotes back diffusion of H+
Antimicrobials found clinically effective against
H.pylori : Amoxicillin, clarithromycin,
metronidazole.
Single drugs rapidly develops resistance
(metronidazole).
 CBS is active against H.pylori and resistance does
not develop to it.

26. Dosage regiment for Anti H.pylori drug
ONE WEEK REGIMENS (mg) TWO WEEK REGIMENS (mg)
Amoxicillin 500 TD/ Clarithromycin 500 TD/Amoxicillin
Clarithromycin 250 BD + 750 BD + Omeprazole 40 OD
Metronidazole 400 TD/ Tinidazole
500 BD + Omeprazole 20 BD
Amoxicillin 500 TD + Amoxicillin 500 TD/ Tetracycline
Clarithromycin 250 TD + 500 QID +Metronidazole 400 QID
Omeprazole 20 BD +Tinidazole 500 BD +
Bismuth 120 QID
Clarithromycin 250 /500 BD + Amoxicillin 750 TD +
Metronidazole 400/ Tinidazole 500 Metronidazole 500 TD +
BD + Lansoprazole 30 BD Ranitidine 300 OD
Amoxicillin 1000 BD + Amoxicillin 1000 BD +
Clarithromycin 500 BD + Clarithromycin 500 BD +
Omeprazole 20 BD Lansoprozoal 30 BD

27. Misoprostol Ranitidine
PGE2 Gastrin
Histamine
+ _ Proglumide
ACh _
M3 _ Adenyl
PGE
cyclase
+ Gastrin
+ receptor + receptor
Ca++ ATP cAMP Ca++
+ + +
Protein Kinase
(Activated)
K+ + H+
Parietal cell
Proton pump
_ Lumen of stomach
Omeprazole _
Gastric acid Antacid

28. REFERENCE
VC Scanlon, Tina ssnders. Essential of Anatomy and
Physiology;5th Edn.2007,F.A.Davis
Company,Philadelphia:376-379.
KD Tripathi. Essentials of medical pharmacology;5th Edn.
2004,Jaypee brothers publication, New Delhi :587-598.
Goodman & Gilman’s. Manual of Pharmacology &
Therapeutics; 11th Edn.2008, MacGraw’s Hill, New york :
621-635.
www.wikepedia/antiulcer.

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